Catalytic enantioselective cyclization/cross-coupling with alkyl electrophiles

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Expanding the scope of cross-coupling reactions with alkyl electrophiles is crucial for organic synthesis.
• Pendant olefins in nucleophilic coupling partners offer opportunities for sequential bond formation.
• Catalytic asymmetric synthesis is vital for producing enantiomerically pure compounds.

Purpose of the Study:

• To develop a novel catalytic asymmetric strategy for synthesizing 2,3-dihydrobenzofurans and indanes.
• To explore the utility of a nickel/diamine catalyzed cross-coupling with pendant olefins.
• To demonstrate the application of this method in constructing complex molecular architectures.

Main Methods:

• Utilizing a nickel/diamine catalyst system for cross-coupling reactions.
• Employing substrates with pendant olefins to facilitate β-migratory insertion.
• Performing catalytic asymmetric synthesis with control over multiple stereocenters.

Main Results:

• Established the viability of the approach for the synthesis of 2,3-dihydrobenzofurans and indanes.
• Successfully applied the method to synthesize the dihydrobenzofuran core of fasiglifam.
• Demonstrated control over two stereocenters, including one newly generated via β-migratory insertion, using a chiral catalyst with a racemic electrophile.

Conclusions:

• The developed method provides an efficient route for catalytic asymmetric synthesis of valuable cyclic compounds.
• This strategy allows for the formation of new C-C bonds and stereocenters, enhancing molecular complexity.
• The approach is applicable to both the synthesis of natural product cores and the stereoselective coupling of racemic substrates.